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Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
Published on: May 7, 2012
Divergent response profile in activated cord blood T cells from first-born child implies birth-order-associated in
M Kragh1, J M Larsen1, A H Thysen2
1Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Insights
First-born infants show a weaker anti-inflammatory response in their T cells at birth. This birth order effect on immune programming may increase their risk for immune-mediated diseases later in life.
Area of Science:
- Immunology
- Developmental Biology
- Pediatrics
Background:
- First-born children have a higher incidence of immune-mediated diseases.
- The mechanisms behind birth-order effects on disease risk are not fully understood.
- In utero programming of the fetal immune system is a potential factor.
Purpose of the Study:
- To investigate the association between birth order and the functional immune response of cord blood T cells.
- To explore how birth order influences T cell activation and cytokine production at birth.
Main Methods:
- Cord blood T cells from 28 infants in the COPSAC2010 cohort were polyclonally activated.
- Flow cytometry assessed activation markers and CD4(+) CD25(+) T cell percentages.
- Cytokine production (IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13, IL-10) was measured.
Main Results:
- First-born infants exhibited significantly reduced IL-10 secretion (P=0.007).
- CD25 expression on CD4(+) helper T cells was also lower in first-borns (P=0.0003).
- Circulating CD4(+) CD25(+) T cell percentages were not affected by birth order.
Conclusions:
- First-born infants present with a less anti-inflammatory T cell profile at birth.
- This suggests potential in utero T-cell programming influenced by birth order.
- Altered immune reactivity in first-borns may contribute to their increased risk of immune-mediated diseases.
Background:
First-born children are at higher risk of developing a range of immune-mediated diseases. The underlying mechanism of 'birth-order effects' on disease risk is largely unknown, but in utero programming of the child's immune system may play a role.
Objective:
We studied the association between birth order and the functional response of stimulated cord blood T cells.
Method:
Purified cord blood T cells were polyclonally activated with anti-CD3-/anti-CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4(+) CD25(+) T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13, and IL-10 was measured in the supernatants.
Results:
IL-10 secretion (P = 0.007) and CD25 expression on CD4(+) helper T cells (P = 0.0003) in the activated cord blood T cells were selectively reduced in first-born children, while the percentage of circulating CD4(+) CD25(+) cord blood T cells was independent of birth order.
Conclusion:
First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero 'birth-order' T-cell programming may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.
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